Cargando…

Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells

The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosu...

Descripción completa

Detalles Bibliográficos
Autores principales: Gong, Yeli, Wang, Zhigang, Liang, Zhihui, Duan, Hongxia, Ouyang, Lichen, Yu, Qian, Xu, Zhe, Shen, Guanxin, Weng, Xiufang, Wu, Xiongwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471819/
https://www.ncbi.nlm.nih.gov/pubmed/23077616
http://dx.doi.org/10.1371/journal.pone.0047435
_version_ 1782246471858388992
author Gong, Yeli
Wang, Zhigang
Liang, Zhihui
Duan, Hongxia
Ouyang, Lichen
Yu, Qian
Xu, Zhe
Shen, Guanxin
Weng, Xiufang
Wu, Xiongwen
author_facet Gong, Yeli
Wang, Zhigang
Liang, Zhihui
Duan, Hongxia
Ouyang, Lichen
Yu, Qian
Xu, Zhe
Shen, Guanxin
Weng, Xiufang
Wu, Xiongwen
author_sort Gong, Yeli
collection PubMed
description The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosuppression can be induced by using MHC-peptide complexes as specific TCR ligand(s) that interact with autoreactive T cells in the absence of co-stimulation. In this study, a soluble divalent MOG35-55/I-A(b) fusion protein (MOG35-55/I-A(b) dimer) was constructed to specifically target the autoreactive CD4(+) T cells in the EAE mouse. Intraperitoneal administration of the MOG35-55/I-A(b) dimer significantly delayed and ameliorated EAE symptoms by reducing EAE-related inflammation in the mouse CNS and reducing encephalitogenic Th1 and Th17 cells in the peripheral lymphoid organs. We observed that dimer intervention at a concentration of 1.2 nM suppressed MOG35-55 peptide-specific 2D2 transgenic T cells (2D2 T cells) proliferation by over 90% after in vitro activation with MOG35-55 peptide. The mechanisms involved in this antigen-specific dimer-mediated suppression were found to be downregulated TCR-CD3 expression as well as upregulated expression of membrane-bound TGF-β (mTGF-β) and IL-10 suppressive cytokines by the autoreactive CD4(+) T cells. Collectively, our data demonstrates that soluble divalent MHC class II molecules can abrogate pathogenic T cells in EAE. Furthermore, our data suggests that this strategy may provide an efficient and clinically useful option to treat autoimmune diseases.
format Online
Article
Text
id pubmed-3471819
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-34718192012-10-17 Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells Gong, Yeli Wang, Zhigang Liang, Zhihui Duan, Hongxia Ouyang, Lichen Yu, Qian Xu, Zhe Shen, Guanxin Weng, Xiufang Wu, Xiongwen PLoS One Research Article The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosuppression can be induced by using MHC-peptide complexes as specific TCR ligand(s) that interact with autoreactive T cells in the absence of co-stimulation. In this study, a soluble divalent MOG35-55/I-A(b) fusion protein (MOG35-55/I-A(b) dimer) was constructed to specifically target the autoreactive CD4(+) T cells in the EAE mouse. Intraperitoneal administration of the MOG35-55/I-A(b) dimer significantly delayed and ameliorated EAE symptoms by reducing EAE-related inflammation in the mouse CNS and reducing encephalitogenic Th1 and Th17 cells in the peripheral lymphoid organs. We observed that dimer intervention at a concentration of 1.2 nM suppressed MOG35-55 peptide-specific 2D2 transgenic T cells (2D2 T cells) proliferation by over 90% after in vitro activation with MOG35-55 peptide. The mechanisms involved in this antigen-specific dimer-mediated suppression were found to be downregulated TCR-CD3 expression as well as upregulated expression of membrane-bound TGF-β (mTGF-β) and IL-10 suppressive cytokines by the autoreactive CD4(+) T cells. Collectively, our data demonstrates that soluble divalent MHC class II molecules can abrogate pathogenic T cells in EAE. Furthermore, our data suggests that this strategy may provide an efficient and clinically useful option to treat autoimmune diseases. Public Library of Science 2012-10-15 /pmc/articles/PMC3471819/ /pubmed/23077616 http://dx.doi.org/10.1371/journal.pone.0047435 Text en © 2012 Gong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gong, Yeli
Wang, Zhigang
Liang, Zhihui
Duan, Hongxia
Ouyang, Lichen
Yu, Qian
Xu, Zhe
Shen, Guanxin
Weng, Xiufang
Wu, Xiongwen
Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells
title Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells
title_full Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells
title_fullStr Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells
title_full_unstemmed Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells
title_short Soluble MOG35-55/I-A(b) Dimers Ameliorate Experimental Autoimmune Encephalomyelitis by Reducing Encephalitogenic T Cells
title_sort soluble mog35-55/i-a(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471819/
https://www.ncbi.nlm.nih.gov/pubmed/23077616
http://dx.doi.org/10.1371/journal.pone.0047435
work_keys_str_mv AT gongyeli solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT wangzhigang solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT liangzhihui solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT duanhongxia solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT ouyanglichen solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT yuqian solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT xuzhe solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT shenguanxin solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT wengxiufang solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells
AT wuxiongwen solublemog3555iabdimersameliorateexperimentalautoimmuneencephalomyelitisbyreducingencephalitogenictcells